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Prophylactic and Therapeutic EBV Vaccines: Major Scientific Obstacles, Historical Progress, and Future Direction.

ABSTRACT: The Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is associated with various malignant tumors and immune diseases, imparting a huge disease burden on the human population. Available EBV vaccines are imminent. Prophylactic vaccines can effectively prevent the spread of infection, whereas therapeutic vaccines mainly stimulate cell-mediated immunity and kill infected cells, thus curbing the development of malignant tumors. Nevertheless, there are still no approved EBV vaccines after decades of effort. The complexity of the EBV life cycle, the lack of appropriate animal models, and the limited reports on adjuvant selection and immune responses are gravely impeding progress in EBV vaccines. The soluble gp350 vaccine could reduce the incidence of infectious mononucleosis (IM), which seemed to offer hope, but could not prevent EBV infection. Continuous research and vaccine trials provide deep insights into the structural biology of viruses, the designs for immunogenicity, and the evolving vaccine platforms. Moreover, the new vaccine candidates are expected to achieve further success via combined immunization to elicit both a dual protection of B cells and epithelial cells, and sustainable immunization against infected cells at several phases of infection.

SUBMITTER: Cai J

PROVIDER: S-EPMC8623587 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEpstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies.MethodsWe searched Cochrane Library, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO's Global Index Medicus, and Google Scholar from inception to June 20, 2020, for EBV prophylactic vaccine studies focused on humoral immunity.ResultsThe search yielded 5,614 unique studies. 36 pre-clinical and 4 clinical studies were included in the analysis after screening against the exclusion criteria. In pre-clinical studies, gp350 was the most commonly used immunogen (33 studies), vaccines were most commonly delivered as monomeric proteins (12 studies), and mice were the most used animal model to test immunogenicity (15 studies). According to an adaptation of the CAMARADES checklist, 4 pre-clinical studies were rated as very high, 5 as high, 13 as moderate quality, 11 as poor, and 3 as very poor. In clinical studies, gp350 was the sole vaccine antigen, delivered in a vaccinia platform (1 study) or as a monomeric protein (3 studies). The present study was registered in PROSPERO (CRD42020198440).ConclusionsFour major obstacles have prevented the development of an effective prophylactic EBV vaccine: undefined correlates of immune protection, lack of knowledge regarding the ideal EBV antigen(s) for vaccination, lack of an appropriate animal model to test vaccine efficacy, and lack of knowledge regarding the ideal vaccine delivery platform. Our analysis supports a multivalent antigenic approach including two or more of the five main glycoproteins involved in viral entry (gp350, gB, gH/gL, gp42) and a multimeric approach to present these antigens. We anticipate that the application of two underused challenge models, rhesus macaques susceptible to rhesus lymphocryptovirus (an EBV homolog) and common marmosets, will permit the establishment of in vivo correlates of immune protection and attainment of more generalizable data.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifier PROSPERO I.D. CRD4202019844.

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Prophylactic and Therapeutic EBV Vaccines: Major Scientific Obstacles, Historical Progress, and Future Direction.

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